The accurate dispensing of small volume liquid samples is of great importance in many industries, particularly the biotechnology industry. Often, large numbers of liquid samples must be analyzed or manufactured. In many such processes in the biotechnology industry, the reagents used are expensive biochemicals. Therefore, it is advantageous to perform the necessary procedures with small quantities of reagent. This has created a demand for machines which can rapidly, accurately and repeatably dispense such small quantities. Typically, sample volumes in the range of 0.1-10 microliters are of interest.
Many prior art devices dispense from a pipette tip which must contact the surface or test tube which receives the sample. In such a device a drop is formed at the pipette tip and then the tip is contacted to the receiving surface or test tube to deposit the drop. This contact method suffers from contamination problems because of the necessity of contact. Such contamination problems are increased if two or more reagents are to be mixed by depositing them in the same test tube. Also, the volume of the dispensed liquid depends upon the surface characteristics of the tip and receiving surface, adversely affecting the volume accuracy. Therefore, it would be an improvement in the art to use noncontact techniques to dispense liquid samples. Noncontact implies that the liquid must be ejected as a free droplet.
Piezoelectric droplet ejectors as commonly used in ink-jet printers are well known in the art and demonstrate a technique for noncontact dispensing of liquids. However, such devices are too large and expensive to use with standard 96-well trays as used in many machines. This would require 96 piezoelectric droplet ejectors. Another problem with this solution is that the largest quantity of liquid that can be ejected is so small that many applications would require hundreds or thousands of droplets. This is time-consuming and relatively inaccurate because the sample size error increases with the number of droplets. Piezoelectric ejectors also have problems relating to reliability and wear.
It is known in the art that a syringe-type positive displacement device comprising a piston inside a pipette can be used to eject liquid samples in a noncontact (projectile) fashion. It is also known that such a device must eject the liquid with a velocity sufficient to overcome the surface tension forces that tend to form the liquid into round droplets (if accurate noncontact dispensing is desired). The formation of round droplets makes it difficult to control the precise volume of liquid dispensed. U.S. Pat. No. 5,525,302 to Astle, for example, discloses an apparatus which can be used in a manner in which the velocity of the ejected liquid is great enough to exceed the surface tension forces. One problem with the device of Astle is that the piston cannot eject the entire quantity of sample liquid inside the pipette in a positive displacement fashion. The narrowing taper at the tip of the pipette prevents the piston from positively displacing and ejecting all the liquid. This is because the piston is not free to move beyond the end of the tube. It is possible to eject the entire quantity of sample liquid by including in the pipette an air bubble and/or a quantity of inert working fluid such as water. However, this considerably complicates the procedure for aspirating and ejecting liquids. Another problem with the Astle invention and tapered pipettes generally is that the taper complicates the relationship between piston position and volume displacement. An accurate, clear relationship between piston position and volume displacement is very important for the dispensing of accurate liquid volumes.
U.S. Pat. No. 3,934,585 to Maurice discloses a device for projectile dispensing of small volumes from a tube tip. However, this invention uses a tube with a tapered tip, i.e. with a reduced diameter toward the end. Therefore, this invention has the same disadvantages associated with tapered tips as described above.
Therefore, there exists a need for a device which can accurately, conveniently and rapidly dispense small volume liquid samples in a noncontact fashion. Further, it would be advantageous for the device to be able to eject all the liquid contained within its pipette in a positive displacement fashion. It would also be advantageous for the device to have an accurate, clear relationship between piston position and volume displacement. The device should be a positive displacement device to provide the accuracy inherent in positive displacement methods.